Chk2 suppresses the oncogenic potential of DNA replication-associated DNA damage

The Mre11 complex (Mre11, Rad50, and Nbs1) and Chk2 have been implicated in the DNA-damage response, an inducible process required for the suppression of malignancy. The Mre11 complex is predominantly required for repair and checkpoint activation in S phase, whereas Chk2 governs apoptosis. We examined the relationship between the Mre11 complex and Chk2 in the DNA-damage response via the establishment of Nbs1(DeltaB/DeltaB) Chk2(-/-) and Mre11(ATLD1/ATLD1) Chk2(-/-) mice. Chk2 deficiency did not modify the checkpoint defects or chromosomal instability of Mre11 complex mutants; however, the double-mutant mice exhibited synergistic defects in DNA-damage-induced p53 regulation and apoptosis. Nbs1(DeltaB/DeltaB) Chk2(-/-) and Mre11(ATLD1/ATLD1) Chk2(-/-) mice were also predisposed to tumors. In contrast, DNA-PKcs-deficient mice, in which G1-specific chromosome breaks are present, did not exhibit synergy with Chk2(-/-) mutants. These data suggest that Chk2 suppresses the oncogenic potential of DNA damage arising during S and G2 phases of the cell cycle.     

Occupancy models including local and landscape variables are useful to assess the distribution of a salamander species at risk

Numerous amphibian species are at risk of extinction worldwide. Therefore, reliable estimations of the distribution and abundance of these species are necessary for their conservation. Generally, amphibians are difficult to detect in the wild, which compromises the accuracy of long-term population monitoring and management. Occupancy models are useful tools to assess how environmental variables, at a local and at a landscape scale, affect the distribution and abundance of organisms taking into account species imperfect detectability. In this study, we evaluated with an environmental multiscale approach the seasonal variation of the occupation area of the threatened salamander, Ambystoma ordinarium along its distribution range. We obtained readings in 60 streams of physicochemical variables associated with habitat quality and landscape features. We found that detection and occupation probability of A. ordinarium are seasonally associated with different environmental variables. During the dry season, detectability was positively associated with temperature and stream depth, whereas occupancy was positively associated with the proportion of crops in the landscape and stream elevation. In the rainy season, the detection probability was not explained by any variable considered, and occupancy was negatively associated with stream's electrical conductivity and dissolved oxygen. Based on the estimation of occupied sites, we showed that A. ordinarium presents a more restricted distribution range than previously projected. Therefore, our results reveal the importance of evaluating the accuracy of distribution estimates for the conservation of threatened species as A. ordinarium.     

CoNi2S4‐Graphene‐2D‐MoSe2 as an Advanced Electrode Material for Supercapacitors

3D CoNi₂S₄‐graphene‐2D‐MoSe₂ (CoNi₂S₄‐G‐MoSe₂) nanocomposite is designed and prepared using a facile ultrasonication and hydrothermal method for supercapacitor (SC) applications. Because of the novel nanocomposite structures and resultant maximized synergistic effect among ultrathin MoSe₂ nanosheets, highly conductive graphene and CoNi₂S₄ nanoparticles, the electrode exhibits rapid electron and ion transport rate and large electroactive surface area, resulting in its amazing electrochemical properties. The CoNi₂S₄‐G‐MoSe₂ electrode demonstrates a maximum specific capacitance of 1141 F g^?1, with capacitance retention of ≈108% after 2000 cycles at a high charge–discharge current density of 20 A g^?1. As to its symmetric device, 109 F g^?1 at a scan rate of 5 mV s^?1 is exhibited. This pioneering work should be helpful in enhancing the capacitive performance of SC materials by designing nanostructures with efficient synergetic effects.     

Assay and characteristics of the iron binding moiety of reticulocyte endocytic vesicles

Summary A⁵⁹Fe assay was designed to detect an Fe(III) binding capacity in NP-40 solubilized proteins from rabbit reticulocyte endocytic vesicles. The iron binding capacity had an apparent molecular weight as determined by gel exclusion chromatography of 450,000 daltons. The iron binding moiety coincided with the major nontransferrin iron-containing material of endocytic vesicles labeled in vivo by incubation of cells with⁵⁹Fe,¹²⁵I-labeled transferrin. The material solubilized from vesicles with NP-40 exhibited two classes of saturable binding sites, one with an association constant for⁵⁹Fe-citrate of 3.63×10⁹ m ^–1 and with 6.6×10^–12 moles of iron bound per mg protein and the other with a constant of 3.96×10⁸ m ^–1 and 1.0×10^–12 moles of iron bound per mg protein. These affinities are sufficient to satisfy the sobulility characteristics of Fe(III) at pH 5.0. Most of the⁵⁹Fe bound both in vivo and in vitro to the iron binding moiety could be displaced with⁵⁶Fe and an equivalent amount of⁵⁹Fe could subsequently be rebound in vitro. The iron binding assay was adopted to vesicle proteins separated by SDS-polyacrylamide gel electrophoresis with subsequent transfer to nitrocellulose and revealed an iron binding activity of molecular weight approximately 95,000 daltons.     

Revealing Complex Ecological Dynamics via Symbolic Regression

Understanding the dynamics of complex ecosystems is a necessary step to maintain and control them. Yet, reverse‐engineering ecological dynamics remains challenging largely due to the very broad class of dynamics that ecosystems may take. Here, this challenge is tackled through symbolic regression, a machine learning method that automatically reverse‐engineers both the model structure and parameters from temporal data. How combining symbolic regression with a “dictionary” of possible ecological functional responses opens the door to correctly reverse‐engineering ecosystem dynamics, even in the case of poorly informative data, is shown. This strategy is validated using both synthetic and experimental data, and it is found that this strategy is promising for the systematic modeling of complex ecological systems.     

Physiological responses of wheat and barley to Russian wheat aphid, Diuraphis noxia (Mordvilko) and bird cherry-oat aphid, Rhopalosiphum padi (L.) (Hemiptera: Aphididae)

Although aphids are among the most injurious of all agronomic insect pests, much remains unknown about how their feeding alters plant physiology. Two experiments were conducted to examine the physiological responses of wheat, Triticum aestivum L. and barley, Hordeum vulgare L. to injury by Diuraphis noxia (Mordvilko) and Rhopalosiphum padi (L.) (Hemiptera: Aphididae). Gas-exchange parameters, chlorophyll fluorescence, and chlorophyll content were examined at 3, 6, and 9 days post-infestation on control and aphid (D. noxia and R. padi) infested treatments. In general, chlorophyll content and chlorophyll fluorescence parameters (non-variable minimal fluorescence, maximal fluorescence, and variable fluorescence) were not significantly affected by either aphid species. Photochemical and non-photochemical quenching coefficients were significantly impacted by both aphid species, suggesting that aphid feeding may influence the photoprotective xanthophyll cycle altering the thylakoid membrane pH gradient. Feeding by both aphid species resulted in an increase in electron transport rate, but at different time periods. Wheat plants infested with D. noxia had accelerated declines in photosynthetic capacity when compared to R. padi-infested and control plants. These plants exhibited decreased values for A_max, which was accompanied by decreased values for V_cmax and J_max Neither aphid species negatively affected the photosynthetic capacity of the barley plants until day 9. At this time, aphid-infested plants had decreased values for A_max which was accompanied by decreased values in J_max. Although R. padi feeding does not typically result in visual damage symptoms as previously demonstrated, clearly this aphid does have an impact on the gas-exchange and chlorophyll fluorescence of its host plants. Handling editor: Heikki Hokkanen     

STING regulates metabolic reprogramming in macrophages via HIF-1α during Brucella infection

Macrophages metabolic reprogramming in response to microbial insults is a major determinant of pathogen growth or containment. Here, we reveal a distinct mechanism by which stimulator of interferon genes (STING), a cytosolic sensor that regulates innate immune responses, contributes to an inflammatory M1-like macrophage profile upon Brucella abortus infection. This metabolic reprogramming is induced by STING-dependent stabilization of hypoxia-inducible factor-1 alpha (HIF-1α), a global regulator of cellular metabolism and innate immune cell functions. HIF-1α stabilization reduces oxidative phosphorylation and increases glycolysis during infection with B. abortus and, likewise, enhances nitric oxide production, inflammasome activation and IL-1β release in infected macrophages. Furthermore, the induction of this inflammatory profile participates in the control of bacterial replication since absence of HIF-1α renders mice more susceptible to B. abortus infection. Mechanistically, activation of STING by B. abortus infection drives the production of mitochondrial reactive oxygen species (mROS) that ultimately influences HIF-1α stabilization. Moreover, STING increases the intracellular succinate concentration in infected macrophages, and succinate pretreatment induces HIF-1α stabilization and IL-1β release independently of its cognate receptor GPR91. Collectively, these data demonstrate a pivotal mechanism in the immunometabolic regulation of macrophages during B. abortus infection that is orchestrated by STING via HIF-1α pathway and highlight the metabolic reprogramming of macrophages as a potential treatment strategy for bacterial infections.     

Modeling of yeast <Emphasis Type="Italic">Brettanomyces bruxellensis</Emphasis> growth at different acetic acid concentrations under aerobic and anaerobic conditions

Glucose utilization by Brettanomyces bruxellensis at different acetic acid concentrations under aerobic and anaerobic conditions was investigated. The presence of the organic acid disturbs the growth and fermentative activity of the yeast when its concentration exceeds 2 g l⁻¹. A mathematical model is proposed for the kinetic behavior analysis of yeast growing in batch culture. A Matlab algorithm was used for estimation of model parameters, whose confidence intervals were also calculated at a 0.95 probability level using a t-Student distribution for f degrees of freedom. The model successfully simulated the batch kinetics observed at different concentrations of acetic acid under both oxygen conditions.